Our aim is to produce new knowledge of the regulation of lung maturation and approaches to prevention and treatment of the lung dysfunction in infancy that may set the stage for chronic lung diseases at a later age. The overall program includes 9 research projects, a biocetry core and an administrative core. We plan to study aspects of surfactant composition and function, including the role of oligopeptides in induction of synthesis; the effects of maternal diabetes on lung maturation with emphasis on fatty acid composition of lung phospholipids and the nature of the lung-specific apoprotein. We will evaluate the effects of substrate restriction on surfactant synthesis using choline as a model. Approaches to therapy of surfactant deficiency include very high frequency mechanical ventilation and the use of artificial surfactants. These interventions will be studied in animal models and evaluated in clinical trials. Our search for an artificial surfactant will include evaluation of protein-free mixtures of surface-active phospholipids. We plan a systematic approach to normal growth and function of lung and chest wall in fetal life through infancy and childhood. The methods include assessment of airway dimensions by acoustic reflections, chest wall mechanics and gas exchange. We will evaluate effects of prenatal administration of dexamethasone on subsequent lung growth and function and will evaluate the long-term consequences of some neonatal lung diseases, such as bronchopulmonary dysplasia.